The long-term objectives of this project are to understand the role of in situ aromatase in breast tumors, and to generate information useful for controlling estrogen biosynthesis in breast cancer patients. Aromatase expression in breast tumor specimens will be evaluated by Southern and DNA slot blot analysis, polymerase chain reactions (PCR), immunohistochemistry, and enzyme activity measurement. The expression level will be correlated with estrogen and progesterone hormone receptor status and several clinico-pathological parameters. Such a study will shed light on the clinical significance of in situ aromatization. Site-directed mutagenesis and active site-labeling experiments will be applied to generate structural information at the active site region of aromatase that can be used in the design of more effective aromatase inhibitors for the treatment of breast cancer. The regulatory mechanism of aromatase expression in breast cancer cells and other estrogen producing cells by hormones, and other reagents will also be investigated. Information generated from this investigation will be very important for further refinements of hormone therapy for breast cancer.